Interstitial ultrasonic disposable applicator and method for tissue thermal conformal volume ablation and monitoring the same

ABSTRACT

An interstitial ultrasound thermal ablation applicator for conformal treatment of inhomogeneous tumor lesions includes: a body having a longitudinal axis, the body defining a hollow central channel along the longitudinal axis; and a plurality of CMUT array transducers mounted on the body, arranged side by side to form a cylindrical shape, having azimuth plans parallel to a longitudinal axis of the body, each of the plurality of CMUT array transducers having elevation dimensions predetermined to steer emitted ultrasonic waves to obtain a conformal volume treatment of the tumor lesions. An electronic driving method for driving an applicator having multiple independent transducer elements arranged in rows and columns includes: controlling focal parameters of each row and column of transducer elements; and controlling a contribution of each row and column of transducer elements in a manner to provide a conformal ablated volume.

CROSS-REFERENCE TO RELATED APPLICATIONS

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STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

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THE NAMES TO PARTIES TO A JOINT RESEARCH AGREEMENT

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INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A COMPACT DISC

Not applicable.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to an ultrasound medical methodand device for interstitial disposable use having multiple ultrasoundcapacitive micromachined ultrasonic transducers (CMUT) to thermallyablate a conformal volume lesion and to monitor the ablated volume withthe same apparatus.

2. Description of Related Art

In recent advances of tumor treatments, surgical methods have progresseda great deal towards minimally invasive techniques to decrease operationmorbidity, pain, and the duration of hospitalization for patients.Minimally invasive procedures such as endoscopy, endovascular surgery orpercutaneous procedures can be accompanied with thermal or cryogenictherapies using probes/applicators that are inserted directly inside orare placed adjacent to the target tissue volume.

Radio Frequency (RF) ablation and Laser Interstitial Thermal Therapy(LITT) have been successfully employed to treat different types ofmetastasis/tumors under MRI guidance. Preliminary results demonstratesignificant improvement of life expectancy, though the current devicescannot be used to create lesions that perfectly match the target volume.Since RF antennas or LITT devices use omnidirectional sources forheating the surrounding tissue, no focusing or steering of the energyradiating pattern can be done without mechanically moving the probe ortreatment devices. Other drawbacks in RF and LITT hyperthermiatreatments are overheating, which occurs for tissue in contact with orin close vicinity of the treatment device, lack of control in lesionhomogeneity due to blood flow, and difficulty in real-time monitoring ofthe therapy.

In thermal ablation, body tissue is exposed to temperatures higher than43° C. for a certain time to damage or kill living cells. High IntensityFocused Ultrasound (HIFU) and High Intensity Contact Ultrasound (HICU)are some types of thermal ablation techniques under investigation forseveral pathologies. Currently piezoelectric-based devices are widelyused to locally heat malignant tissue. However, currentpiezoelectric-based HIFU/HICU applicators show undesirable effects andshortcomings such as local tissue overheating at the transducer tissueinterface and lack of control for the treatment volume (risk of ablationof healthy tissue or under treatment). In particular, in braintherapies, the treatment of pathologic tissue (tumor) requires a smalldiameter needle shaped applicator (maximum 3-4 mm) to access the site oftreatment with minimal damage to the surrounding tissue and interstitialprocedures provide the advantage of more accurate control of the ablatedvolume as well as the assurance of avoiding damage for healthy tissuesince the HIFU/HICU source is located at the center of the tissues to beablated. Current surgical products for interstitial HIFU/HICU proceduresexhibit limited ablation capability features (focusing, conformalvolume) and all require an active cooling system to avoid overheating oftissue in contact with the ultrasound source and therefore cannot beplaced in direct contact with biologic tissue. Finally, current productsmay not exhibit optimal MR compatibility since artifacts may occur dueto the presence of air bubbles, metal parts etc.

The above described difficulties led to the need for the development ofalternative methods and apparatus that can be used to produce morehomogeneous lesions with conformal treatment volumes for tumors andhaving the capability of real time monitoring or the measuring ofphysical and/or physiological functions/parameters of the organ orablated tissue during operation. Prior art references directed toconformal treatment and or combined treatment/monitoring proceduresinclude the following relevant documents as follows.

European Patent Application Publication No. 0 643 982 A1 (Burdette etal.) and International Patent Application Publication No. WO2007/124458A2 (Diederich et al.) relate to a device and a method for treatment ofprostatic or uterine tissue. Typically the ultrasound transducers aremounted inside a delivery system housing that prevents the emittingdevices from directly contacting the tissue during operation.Multi-segment transducers can be used and a combination of multipletransducer arrangements can provide focusing of the acoustic energy.Unfortunately, the apparatus as described still requires cooling fluidto be circulated inside said delivery system to regulate the temperatureof the probe. Furthermore, no conformal volume treatment methodology isdescribed therein.

Similarly, in International Patent Application Publication No. WO2009/125002 A1 (Carpentier et al.), where a percutaneous MRI compatibleprobe is disclosed for medical systems, the probe is describedcomprising a longitudinal body to be inserted into the body and having aplurality of ultrasonic transducers designed for focused and non-focusedtherapeutic ultrasound with an aspiration channel passing through theprobe body longitudinally. The transducers can be arranged bothlongitudinally and circumferentially. A fluid-based cooling system isprovided to control the temperature of the device. While transducers canbe easily arranged longitudinally to form a linear phased array incircumference, it is not clear how the probe can achieve any focusingsince the number of sectors is limited and no indication is provided formaking it. No detail is disclosed for conformal volume treatment and theprobe still requires a cooling system.

In U.S. Pat. No. 7,494,467 (Makin et al.) an ultrasonic and RF combinedmedical system is disclosed. In some embodiments, imaging transducersare combined with therapy transducers to monitor the tissue ablated.However none of the embodiments described can produce conformalvolumetric lesions and, furthermore, the design requires the apparatusto be rotated or moved to treat or monitor a volume.

U.S. Pat. No. 5,697,897 (Buchholtz et al.) describes a therapeuticendoscope having a single linear array ultrasonic transducer mounted inthe longitudinal axis for treatment and diagnosis. In one embodiment,the diagnostic transducer can be separate from the one for therapy. Thedocument disclosure is limited to one plane focusing and requires theapparatus to be rotated to achieve a volume treatment.

U.S. Patent Application Publication No. US WO 02/32506 A1 and U.S.Patent Application Publication No. US 2006/0206105 A1 (Chopra et al.)disclose a thermal therapy device using a multi-element ultrasoundheating applicator. The ultrasonic applicator is located under anacoustic window. The ultrasonic transducer can be electronicallyactivated to cover the geometry of the treated area in a 2D plane, and avolumetric lesion (3D) can be obtained by rotating or moving theapparatus. The applicator has the capability for varying the power andswitching the frequency of each ultrasound element enabling thetemperature to be adjusted both radially and along the length of theapplicator. However, the frequency control is limited to switchingbetween discrete frequencies within multiple narrowband harmonics of thefundamental.

U.S. Pat. No. 6,379,320 (Lafon et al.) describes an ultrasonicapplicator for intra tissue heating wherein a planar emitting surface isprovided within the applicator head and is separated from the tissue tobe treated by a sealed membrane. The space between the ultrasonic deviceand the membrane is filled with liquid which also serves as temperatureregulation for the applicator. The applicator has no focusing orsteering capability, so the treatment volume will only be obtained byrotating the applicator on site.

European Patent Application Publication No. 1,090,658 (Rabiner et al.)discloses methods or structures which include improvements over theabove application requirements. However a number of problems stillremain unsolved regarding, specifically, a conformal volume treatmentmethod, a dedicated ultrasonic thermal ablation device, and a method ofmaking the same.

BRIEF SUMMARY OF THE INVENTION

It is an object of the invention to provide an improved ultrasonicthermal ablation applicator for treatment of inhomogeneous lesions andfor conformal volume ablation using a particular configuration ofultrasonic transducers that allows interstitial use and direct contactof the ablation source and the tissue to be treated.

It is another object of the invention to provide an improved ultrasonicthermal ablation applicator having independent linear array transducermodules assembled side by side to form a cylindrical source and having apredetermined width to achieve smooth conformal volume ablation.

It is another object of the invention to provide an improved ultrasonicthermal ablation applicator having a broad bandwidth (e.g. 2-30 MHz)which can be used to modulate the driving frequency during thermalablation procedures for conformal volume ablation.

It is further an object of the invention to provide an improvedultrasonic thermal ablation applicator for conformal volume ablation andhaving a hollow central canal that provides access to the pathologicaltissue and secondary to the treatment materials, and which can be usedfor delivering in situ drugs or imaging contrast agents.

It is still another object of the invention to provide an improvedultrasonic thermal ablation applicator and method for limiting thenumber of electrical interconnections when focusing and steering theultrasound energy in the region of interest/treatment.

It is another object of the invention to provide an improved ultrasonicthermal ablation applicator and method wherein both the alternating anddirect excitation voltages can be independently modulated to controlboth the magnitude and spatial characteristics of the acoustic output ofthe device.

It is another object of the invention to provide a manufacturing methodaccording to the said improved ultrasonic thermal ablation applicatorwherein an inner removable rigid spindle or shaft is provided within thecentral hollow channel to rigidify the probe during itsmanufacturing/assembling and for tissue implantation.

It is another object of the invention to provide an improved ultrasonicthermal ablation applicator in direct contact with the tissues, whereinthe transducer devices are equipped with integrated biosensors formonitoring the metabolic status of the tissue before treatment.

It is another object of the invention to provide an improved ultrasonicthermal ablation applicator in direct contact with the tissues, whereinthe transducer devices are equipped with integrated nano laseroscillator emitters to allow in vivo sub-cellular tissue identificationby near-infrared multi photon-induced auto fluorescence microscopy, andto allow photo sensitive nanoparticle delivery.

It is another object of the invention to provide an improved ultrasonicthermal ablation applicator in direct contact with the tissues, whereinthe transducer devices are equipped with integrated temperature sensorsand or integrated pressure sensors and or microelectrodes for monitoringthe physiological functions of the organ during treatment.

It is another object of the invention to provide an improved ultrasonicthermal ablation applicator in direct contact with the tissues, whereinthe transducer devices perform Doppler imaging of the tissuevascularization before and after the treatment for a revascularizationefficacy proof.

According to one aspect of the invention, an interstitial ultrasoundthermal ablation applicator for conformal treatment of inhomogeneoustumor lesions includes: a body having a longitudinal needle shape and alongitudinal axis, the body defining a hollow central channel along thelongitudinal axis, the hollow central channel serving as a passage forbiopsy needles or tools for aspiration of biologic materials orproviding in-situ drug delivery; and a plurality of capacitivemicromachined ultrasonic transducer (CMUT) array transducers mounted onsaid body, arranged side by side to form a cylindrical shape, havingazimuth plans parallel to a longitudinal axis of the body, each of theplurality of CMUT array transducers having elevation dimensionspredetermined to steer emitted ultrasonic waves to obtain a conformalvolume treatment of the tumor lesions.

In one implementation, each of the plurality of CMUT array transducersincludes an emitting surface covered with an electrically insulatingprotective layer such that the interstitial ultrasound thermal ablationapplicator can be placed in direct contact with the tissue.

In another implementation, the elevation dimensions of each of theplurality of CMUT array transducers are no larger than three (3)wavelengths.

Each of the plurality of CMUT array transducers may include a siliconsubstrate, such that the device is MRI compatible due to the siliconsubstrates.

Further, the plurality of CMUT array transducers may have a thickness ofless than 100 microns, and are flexible so as to conform an externalsurface of the body.

Additionally, the interstitial ultrasound thermal ablation applicatormay further include a biocompatible protection film covering the bodyand the plurality of CMUT array transducers.

According to another aspect of the invention, an interstitial ultrasoundthermal ablation applicator for the treatment of inhomogeneous tumorlesions, includes: a body having a longitudinal needle shape and alongitudinal axis; a plurality of capacitive micromachined ultrasonictransducer (CMUT) linear array transducers mounted on said body,arranged side by side to form a cylindrical shape, having azimuth plansparallel to the longitudinal axis of the body, each of the plurality ofCMUT linear array transducers having elevation dimensions predeterminedto steer emitted ultrasonic waves to control smoothness of a resultingablation volume; and at least one of an integrated sensor and anintegrated sensing device to monitor at least one of a physicalparameter and a physiological parameter of an organ.

In further implementations, at least one of an integrated sensor and anintegrated sensing device is one or more of the following: a temperaturesensor; a pressure sensor; a gas sensor; a biosensor; and a laseremitter.

According to yet another aspect of the invention, an interstitialultrasound thermal ablation applicator for the treatment ofinhomogeneous tumor lesions, includes: a body having a longitudinalcatheter shape and a longitudinal axis; a plurality of capacitivemicromachined ultrasonic transducer (CMUT) linear array transducersmounted on said body, arranged side by side to form a cylindrical shape,having azimuth plans parallel to the longitudinal axis of the body, eachof the plurality of CMUT linear array transducers having elevationdimensions predetermined to steer emitted ultrasonic waves to controlsmoothness of a resulting ablation volume; an integrated sensor formonitoring at least one of a physical parameter and a physiologicalparameter of an organ; and an integrated Lab-on-Chip (LoC) devicelocated within a surface of one of the plurality of CMUT linear arraytransducers for in-situ analyzing of tissue.

In one implementation, the LoC device is a microfluidic device for oneof cytometry assays and biological assays.

Another aspect of the invention is an electronic driving method fordriving an interstitial ultrasound thermal ablation applicator havingmultiple independent transducer elements arranged in rows and columnsdisposed on a periphery of the interstitial ultrasound thermal ablationapplicator. The method includes: controlling focal parameters of eachrow and column of transducer elements; and controlling a contribution ofeach row and column of transducer elements in a manner to provide aconformal ablated volume.

In one implementation, the method further includes: shuntingelectrically adjacent transducer elements two by two in each respectiverow; and controlling the transducer elements in columns independently toachieve conformal volume sonication/treatment.

In another implementation, the method further includes: shuntingtogether top electrodes of the transducer elements in each respectiverow, such that all rows are electrically isolated; shunting togetherbottom electrodes of the transducers in each respective column, suchthat all columns are electrically isolated; and activating a desiredtransducer element by connecting the top electrodes of a selected rowand the bottom electrodes of a selected column to a power supplysimultaneously to polarize the desired transducer element located inboth the selected row and the selected column.

In yet another implementation, the rows are disposed symmetrically witha symmetry line at a middle of the interstitial ultrasound thermalablation applicator, wherein the rows are arranged in a position orderfrom P₁ to P_(N) and Q_(N) to Q₁, respectively, around the symmetryline. The method then includes: shunting together top electrodes of thetransducer elements forming a row P_(X) and a row Q_(X) of same order,such that rows of different orders are electrically isolated; arrangingrows P and rows Q in reverse chronology so as to obtain the last orderrow P_(N) adjacent to the last order row Q_(N) and therefor first orderrow P₁ and first order Q₁ are located at opposite ends of theinterstitial ultrasound thermal ablation applicator; shunting togetherbottom electrodes of transducer elements forming in each respectivecolumn, such that all columns are electrically isolated; and activatinga desired transducer element by connecting the top electrodes of aselected row and the bottom electrodes of a selected column to a powersupply simultaneously to polarize the desired transducer element locatedin both the selected row and the selected column.

According to yet another aspect of the invention, a method of providingthermal ablation of a tissue region by an interstitial procedure usingan interstitial ultrasound thermal ablation applicator comprising aplurality of ultrasonic transducers, includes: inserting and positioningthe interstitial ultrasound thermal ablation applicator at a center ofone of incriminated tissue and a tumor; applying electrical actuationindividually to the plurality of ultrasonic transducers, each of theplurality of ultrasonic transducers having respective custom focalcharacteristics; controlling ultrasonic energy supplied and treatmentduration for each of the plurality of ultrasonic transducers to controltissue temperature elevation and distribution; and removing ablatedmaterial from a treatment site for assessment.

According to another aspect of the invention, a method of providingthermal ablation of a tissue region by an interstitial procedure usingan interstitial ultrasound thermal ablation applicator comprising aplurality of ultrasonic transducers, includes: inserting and positioningthe interstitial ultrasound thermal ablation applicator at a center ofone of incriminated tissue and a tumor; applying electrical actuationindividually to the plurality of ultrasonic transducers, each of theplurality of ultrasonic transducers having respective custom focalcharacteristics; controlling ultrasonic power supplied; controlling thefrequency and phase of said supply ultrasonic energy and controllingtreatment duration for each of the plurality of ultrasonic transducersto control tissue temperature elevation and distribution; and removingablated material from a treatment site for assessment.

In one important implementation, the procedure is performed undermagnetic resonance imaging (MRI) scanning to monitor local temperatures.

In one important implementation, the treatment procedure is performedusing at least one of those strategies: Power Modulation (PM), FrequencyModulation (FM) or Phase Modulation (PhM) of the ultrasound wavegenerated by each independent element to adjust, based on MR-thermometryfeedback control, the amount and location of the heat deposited in the3D volume surrounding the applicator.

In another important implementation, the interstitial ultrasound thermalablation applicator has a needle shape with a diameter smaller than 4 mmso as to not damage healthy tissue during insertion.

Other features and advantages of the invention will be set forth in, orapparent from, the detailed description of exemplary embodiments of theinvention found below.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A, 1B, and 1C are a sequence of figures illustrating an exemplaryprocedure for tumor interstitial treatment according to the invention.

FIG. 2 is a graphical view of a section of a treatment volume of aconformal lesion.

FIGS. 3, 4, and 5 show several embodiments of an exemplary interstitialultrasound thermal ablation applicator according to the invention.

FIGS. 6A through 6D are graphical renderings of examples of 3D conformalvolumes obtained using an exemplary thermal ablation applicatoraccording to the invention.

FIG. 7 is a side sectional view of an internal structure of an exemplarycapacitive micromachined ultrasonic transducer (CMUT), according to theinvention.

FIG. 8 is a perspective view of another embodiment of an exemplarythermal ablation applicator.

FIG. 8A is an enlarged view of a proximal end of the exemplary thermalablation applicator as identified by the broken lines labeled 8A in FIG.8.

FIG. 9A is a sectional view showing one assembly of the exemplarythermal ablation applicator taken at the plane identified as 9-9 in FIG.8.

FIG. 9B is a sectional view showing another assembly of the exemplarythermal ablation applicator taken at the plane identified as 9-9 in FIG.8.

FIG. 10 is a perspective view of another embodiment of an exemplarythermal ablation applicator.

FIG. 11 is a perspective view of another embodiment of an exemplarythermal ablation applicator.

FIGS. 12, 13A, and 13B are functional block diagrams of an electricalsystem of an interstitial ultrasonic disposable applicator, according tothe invention.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS OF THE INVENTION

The details of one or more embodiments of the presently-disclosedsubject matter are set forth in this document. Modifications toembodiments described in this document, and other embodiments, will beevident to those of ordinary skill in the art after a study of theinformation provided in this document. The information provided in thisdocument, and particularly the specific details of the describedexemplary embodiments, is provided primarily for clearness ofunderstanding and no unnecessary limitations are to be understoodtherefrom. In case of conflict, the specification of this document,including definitions, will control.

While the following terms are believed to be well understood by one ofordinary skill in the art, definitions are set forth to facilitateexplanation of the presently-disclosed subject matter.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which the presently-disclosed subject matter belongs.Although any methods, devices, and materials similar or equivalent tothose described herein can be used in the practice or testing of thepresently-disclosed subject matter, representative methods, devices, andmaterials are now described.

Following long-standing patent law convention, the terms “a”, “an”, and“the” refer to “one or more” when used in this application, includingthe claims. Thus, for example, reference to “a cell” includes aplurality of such cells, and so forth.

Unless otherwise indicated, all numbers expressing quantities ofingredients, properties such as reaction conditions, and so forth usedin the specification and claims are to be understood as being modifiedin all instances by the term “about.” Accordingly, unless indicated tothe contrary, the numerical parameters set forth in this specificationand claims are approximations that can vary depending upon the desiredproperties sought to be obtained by the presently-disclosed subjectmatter.

As used herein, the term “about,” when referring to a value or to anamount of mass, weight, time, volume, concentration or percentage ismeant to encompass variations of in some embodiments ±20%, in someembodiments ±10%, in some embodiments ±5%, in some embodiments ±1%, insome embodiments ±0.5%, and in some embodiments ±0.1% from the specifiedamount, as such variations are appropriate to perform the disclosedsubject matter.

As used herein, ranges can be expressed as from “about” one particularvalue, and/or to “about” another particular value. It is also understoodthat there are a number of values disclosed herein, and that each valueis also herein disclosed as “about” that particular value in addition tothe value itself. For example, if the value “10” is disclosed, then“about 10” is also disclosed. It is also understood that each unitbetween two particular units are also disclosed. For example, if 10 and15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

The terms “array transducer” or “transducer array” are used herein todescribe a transducer device obtained by geometric arrangement of aplurality of individual transducers (i.e., transducer elements) havingdimensions compatible with desired ultrasonic beam focusing and steeringfeatures.

The term “linear array” is generally used to describe a one-dimensionalarray and can be applied to arrays with flat or curved shapes.

The terms “element transducer” or “transducer element” or “transducer”are used herein to describe an individual ultrasonic transducercomponent of an array transducer. Generally, an element transducer of anarray transducer has planar dimensions suitable for electronic steeringand focusing of ultrasonic beams.

The present invention relates to a method and an apparatus for thermalconformal ablation. It should be noted that the invention is not limitedto the description or arrangement illustrated in the accompanyingdrawings and description. It is also understood that any embodiments canbe combined with the other embodiments or can be implemented into otherapparatus with no change in the principle. Another major aspect of thepresent invention relates to the compatibility of the ablation device tobe used under MRI imaging/monitoring with acceptable artifacts; thiswill be performed by the utilization of non-metallic materials andabsence of air volume within the device body.

Referring to the method of the invention, the embodiment of FIGS. 1A,1B, and 1C illustrate steps of an interstitial thermal ablationprocedure by high intensity focused ultrasound (HIFU) or high intensitycontact ultrasound (HICU) that can be used to treat cancerous ornon-cancerous tumors and more particularly can be advantageously appliedto brain tumor treatment. With HIFU, the therapeutic depth depends onthe exposure conditions in general but more particularly on theoperating frequency. Broadband CMUT transducers are advantageous as theyallow performing conformal ablation by adjusting the depth of treatmentwith the operating frequency. cMUT transducers allow using FrequencyModulation (FM) strategies over a broad continuous spectrum (e.g. 2-30MHz) for precise optimization of the ultrasonic frequencies as afunction of the targeted tissue depths. Multiple independent broadbandcMUT elements integrated on the same applicator allow combining multipleultrasound beams at various frequencies over a broad continuous spectrum(e.g. 2-30 MHz) for performing conformal thermal ablation. Adjuvant drugdelivery can also be achieved with CMUT transducers emitting lowfrequency waves.

FIG. 1A shows a thermal ablation applicator 4 inserted into brain tissue2 by hole 6 created through a skull 1. The applicator 4 penetrates thebrain tissue 2 to reach a malignant tumor 3 to be treated. Theapplicator 4 defines a hollow channel 5 and an opening 7 located at thedistal end of the applicator 4. The hollow channel 5 has a diameter thatis large enough to accommodate a diameter of a biopsy mandrel 8 (FIG.1B). Alternately, the applicator 4 can be inserted into the brain tissue2 with the biopsy mandrel 8 (FIG. 1B) in position in a manner to providemore stiffness to the applicator 4.

FIG. 1B shows a biopsy mandrel 8 inserted into the malignant tumor 3 fortissue extraction or analysis.

FIG. 1C shows the applicator 4 inserted through the malignant tumor 3.Preferably, the applicator is inserted without moving the biopsy mandrelsuch that a tumor sample is then trapped into the biopsy mandrel 8. Thebiopsy mandrel 8 is then removed from the applicator for tissueextraction or analysis without further moving the applicator. Inaddition, by removing the biopsy mandrel 8, the biopsy mandrel 8 willnot disturb (i.e., create artifacts) the monitoring of the malignanttumor 3 under Magnetic Resonance Imaging (MRI) for upcoming treatment.After checking for proper positioning of the applicator 4 by a new MRIsequence, a treatment simulation is performed and, further, thetreatment itself started.

The medical procedure as depicted in FIGS. 1A, 1B and 1C is well adaptedfor brain tumor treatment since the diameter of the applicator 4 remainsreasonable (3 mm-4 mm) and the applicator 4 is MRI compatible.Furthermore, the hollow channel 5 enables physicians to extract ablatedtissue from the tumor. Once the treatment procedure is complete andmonitored with MRI or ultrasonic imaging, an aspiration of a liquefiedportion of treated tissue can be drawn through the hollow channel 5 fromthe opening 7 of the applicator 4. At the end of the procedure, theapplicator 4 is removed from the brain tissue 2 and a stitch isperformed on the skin for closing.

For carrying out the medical procedure as explained in FIG. 1A to FIG.1C, the applicator 4 is equipped with a plurality of ultrasonic arraytransducers arranged and symmetrically disposed around and along alongitudinal axis of the applicator 4 to provide a 360 degree ultrasonicsonication. Such an applicator 4 suitable for treatment of a malignanttumor 3 will be further described in more detail below. The applicator 4and method use multi-focused ultrasound to obtain a conformal volumetreatment of tumor tissue regions.

FIG. 2 is a graph of a numerical modeling performed using an exemplaryapplicator having eight faces in a polygonal arrangement. As shown inFIG. 2, a smooth volume can be achieved by using independent control ofthe arrays and taking into account the acoustic absorption and thermalconductivity of the tissue, and lesion boundary conditions.

As shown in FIG. 12, each transducer Tx1, Tx2, Tx3, . . . Tx(N−2),Tx(N−1), T×N is connected to independent driving electronics (i.e.,controllers) C1, C2, C3, . . . C(N−2), C(N−1), CN that may consist ofelectrical impedance matching networks and DC bias controller, and whichmay be controlled by a system mainframe 1200 in communication with anoutput power management system 1202 that controls the amplitude (A_(N)),frequency (f_(N)) and phase (φN) for each individual element forelectronic focusing or steering. As shown schematically, theconfiguration is repeated for M arrays.

In another configuration, as shown in FIG. 13 a, the electronic drivingsystem may include a separate DC bias controller 1201 for activation ofspecific subgroups of elements or arrays of the device that allows for arow-column control system. In this configuration, the DC bias voltagelevel delivered to a specific subgroup of elements may be used tomodulate the acoustic output of a specific subgroup of elements thathave a common bottom electrode. To achieve this configuration, theelements are wired electrically according to the configuration shown inFIG. 13 b, where the AC driving voltage is applied at the top electrodeto a single element or group of elements and the DC bias voltage isapplied at the bottom electrode. In this configuration, the bottomelectrode may be common to a single element, several elements, oneentire linear array of the transducer, or to all of the elements of thetransducer.

The advantage of using a CMUT device for high intensity ultrasound isits intrinsic absence of self-heating during long (several seconds toseveral minutes) and continuous driving operations. Indeed,electrostatic vibration forces created by capacitive membranes are basedon voltage variations with no need for current intensity. Since a cavitygap is vacuum sealed, low parasitic capacitance is expected so aself-heating effect is therefore negligible as well.

FIG. 7 is a sectional view of an exemplary CMUT cell 21, which isdescribed in more detail below.

FIGS. 3, 4 and 5, show exemplary configurations for array transducers(e.g., FIG. 12, Tx1, Tx2, Tx3, . . . Tx(N−2), Tx(N−1), T×N, for Marrays) mounted on an exemplary thermal ablation applicator 4 (see FIG.1A-FIG. 1C) to perform conformal volume ablation. The purpose of thisarray configuration is to achieve optimal tissue ablation efficiencyunder accurate volume control while limiting the number of independentdriving channels at reasonable numbers (e.g., 64) for mastering of costand design complexity.

As a non-limiting example, FIG. 3 shows an array configuration of thethermal ablation applicator 4 comprising an assembly of ten transducerarrays 17 (i.e., columns of transducer elements 18, also referred to asarray transducers) arranged in a polygonal manner. Each of thetransducer arrays 17 preferably includes a plurality of transducerelements 18, which can be either identical to each other or undercustomized specifications with no change in principle. Preferably, allof the transducer arrays 17 are identical geometrically and, forsimplicity, the transducer elements 18 operate at a resonance frequencythat maximizes a ratio between output energy and penetration. Forexample, an optimal frequency range is from about 3 to 10 MHz and anoptimal acoustic surface intensity is between about 10-30 watts/cm² fora tumor having a diameter of around 30 mm. Such frequency range andoutput acoustic intensity are here given as an example and should not beconsidered as design limitations for the present invention, as othercombinations of frequency/intensity may be applied to the description ofthe invention with no change in the principle thereof.

Still referring to the array configuration of FIG. 3, the transducerelements 18 are electrically connected or shunted by pair (two adjacenttransducer elements 18 are to be connected together) in a transversesectional plan of the applicator 4, as highlighted in the figure. Theshunting of adjacent transducer elements 18 reduces the number of activechannels while keeping smooth polygon angles for the applicator 4. As isshown, the applicator 4 comprises a plurality of rows 19 of transducerelements 18, each of the rows 19 of transducers formed by severaltransducer elements 18 shunted two by two in order to reduce the numberof connections. For clarity of the description, the applicator of FIG. 3is preferably composed of ten transducer arrays 17 (i.e., columns oftransducer elements) and twelve rows 19 of transducer elements (not allshown). The number of transducer arrays 17 equates to the number oftransducer elements 18 in each row 19. As the adjacent transducerelements 18 in each row 19 are shunted two by two, the number ofelectrical connections is reduced to sixty instead of one hundredtwenty.

FIG. 6A through FIG. 6D are graphs of modeling results of conformalvolumes obtained with a configuration of transducer arrays 17 mounted onan exemplary thermal ablation applicator 4, such as described above.

FIG. 6A shows an example of a 3D complex volume 41 (i.e., heating volumeshape or ablated lesion volume) that is obtained using such anapplicator 4. In this example the acoustic power is independentlyprogrammed for each transducer element 18 (FIGS. 3-5) to achieved thedesired 3D complex volume 41 (i.e., heating volume shape or ablatedlesion volume).

FIG. 6B is a sectional view of the exemplary ablated lesion volume 41with thermal doses spreading around such an applicator 4. This graphclearly indicates the capability of such an applicator 4 to providelocalized and well-controlled thermal dose distribution to lesion tissuein a 3D complex volume (i.e., heating volume shape).

FIG. 6C is a longitudinal view of the exemplary ablated lesion volume 41of FIG. 6B, showing thermal doses distribution around such an applicator4. The asymmetrical distribution shown in this figure and in FIG. 6Billustrate conformal volume treatment.

FIG. 6D shows an example of a different 3D complex volume 42 that isobtained using such an applicator 4 with twelve (12) transducer arraysoperated at 6 MHz. For better description of the volume treated, theillustration of FIG. 6D only shows the ½ volume with its symmetricalsectional face (the whole volume is to be considered when treated withall transducers in operation). An output acoustic power sufficient togenerate a surface intensity of 20 W/cm² is applied at the surface ofarray transducer under the following sequence: 105 seconds ON.

The exemplary thermal ablation applicator 4 of the invention may alsoadvantageously utilize continuous Frequency Modulation (FM) to controltissue penetration and thermal dose distribution since the CMUToperations are sensitive within a large frequency range. FM strategiescan be applied on each electrically independent cMUT transducer tocontrol ultrasonic frequencies over a broad continuous spectrum andachieve simultaneously various treatment depths in 3D. In other words,the transducers elements 18 and by extension the transducer arrays 17can be excited at different frequencies so as to better fit tissueablation requirements and conditions, or to emphasize the conformaleffect by the possibility of applying a particular emitting frequency oneach transducer element 18 or transducer array 17.

More particularly, as shown in FIG. 7, an exemplary CMUT cell 21according to the invention includes a membrane 23 that is excited byoscillations of electrostatic forces exerted via a bottom electrode 24and an opposing top electrode 25. The electrostatic forces are createdby an electrical field exerted between the opposite electrodes 24 and 25and a capacitance value is controlled by a gap of a sealed cavity 26(i.e., a capacitance gap) these electrostatic forces are governed by thefollowing equation

Fe=−Sε0V ² /z ²  (1)

that can be developed to obtain

$\begin{matrix}{{Fe} = {{- S}\; ɛ\; 0\frac{\left( {{V\; 0} + {V\; 1}} \right)^{2}}{z\; 0^{2}\left( {1 + \left( {u\; {1/z}\; 0} \right)^{2}} \right)}}} & (2)\end{matrix}$

wherein V0 represents the DC voltage and V1 represents the AC voltageapplied to the CMUT for oscillation; finally the previous equation canbe developed into fundamental and harmonic terms as follows

$\begin{matrix}{\frac{F}{S\; ɛ\; 0} = {\frac{\left( {V\; 0} \right)^{2}}{\left( {z\; 0} \right)^{2}} + {2\frac{\left( {V\; 0V\; 1} \right)}{\left( {z\; 0} \right)^{2}}} + \frac{\left( {V\; 1} \right)^{2}}{\left( {z\; 0} \right)^{2}} + {u\; 1\frac{\left( {V\; 0} \right)^{2}}{\left( {z\; 0} \right)3}} + {{higher}\mspace{14mu} {{terms}.}}}} & (3)\end{matrix}$

Here one can see that the first term corresponds to the static force,the second term drives

$\begin{matrix}\left( {2\frac{\left( {V\; 0\; V\; 1} \right)}{\left( {z\; 0} \right)^{2}}} \right) & (4)\end{matrix}$

the membrane in fundamental mode with a maximum of energy and the thirdand other higher terms contribute to harmonic modes, based on the abovedescription it is important to notice that under absence of DC voltage(V0=0) only harmonic modes are excited and are much less energetic thanthe fundamental one. In transmission mode, excitation voltageoscillations are converted into alternative electrostatic forces tovibrate the membrane 23 (emission of ultrasonic waves). In receivingmode, mechanical forces applied on transducer cause the membrane 23 todeflect, move, or deform, and modify the gap of the sealed cavity 26.Then a voltage variation is measured between the bottom electrode 24 andthe top electrode 25. The structure of the exemplary CMUT cell 21desired is formed on a silicon substrate 22 (and an oxide layer 22 a),but other materials such as glass or polymers may be utilized as a basestructure as well. Other complementary layers can be added to theexemplary CMUT cell 21 to provide better protection or to improveacoustic performance of the structure. However, the operationalprinciple of the CMUT cell 21 is substantially as described herein.

In another embodiment as shown in FIG. 4 an exemplary thermal ablationapplicator 4 includes transducer arrays 17 (columns of transducerelements 18) and rows 19 of transducer elements 18, as in the embodimentof FIG. 3. However, in the embodiment of FIG. 4, the top electrodes (seeFIG. 7, top electrode 25) of the endmost row 19 a of transducer elements18 are connected together. The bottom electrodes (see FIG. 7, bottomelectrode 24) of the transducer elements 18 of a preselected transducerarray 17 a (i.e., column of transducer elements 18) are also connectedtogether. Each of the transducer elements 18 (i.e., a CMUT cell 21 (FIG.7)) needs to be polarized via its opposite electrodes to operate.Therefore, the control of a selected transducer element 18 a on theexemplary thermal ablation applicator 4 is obtained by selecting theparticular transducer array 17 a (i.e., column) and the particular row19 a of transducer elements 18 of the selected transducer element 18 a,and applying a voltage excitation function with suitable frequency(typically 6 MHz but can also be adjusted in the range of 3-10 MHz) andacoustic surface intensities (from 5 to 20 w/cm²) across thecorresponding bottom electrodes and top electrodes to produce thedesired ultrasonic vibration effect.

The exemplary applicator 4 of FIG. 4 further has the top electrodes ofeach respective row 19 of transducer elements 18 connected together, andthe bottom electrodes of each respective transducer array (i.e. column)of transducer elements 18 connected together. Advantageously, this arrayconfiguration reduces the number of connections required forpolarization of individual transducer elements 18 to control the activesurface of the applicator 4. Indeed, as operation in CMUT devices isgoverned by the bias voltage applied between the two opposite electrodesof the device as described in detail in the previous section relating toFIG. 7. This voltage will pre-stress the CMUT to react to any voltagevariation by moving the membrane to modify the capacitance gapaccordingly. This, consequently, also creates ultrasonic waves. For oneskilled in the art, only the surface area of transducer that is coveredby the involving bottom and top electrodes is energized or sensitive tomechanical pressure in receiving mode as previously explained. Thus,this structure and method enables control of any of the individualtransducer elements 18 of the exemplary thermal ablation applicator 4 byapplying suitable voltage to the corresponding top electrode 25 andbottom electrode 24 (see: FIG. 7). The number of control connectionswill then depend on the number of independent columns (n) (transducerarrays 17) and rows (m) (rows 19 of transducer elements 18) to becontrolled. In other words, all of the transducer elements 18 of thearray configuration can be individually address using n+m controlconnections instead of n×m control connections to connect eachtransducer element separately.

Similarly, FIG. 5 shows another exemplary thermal ablation applicator 4which is composed of rows 19 b on one end and rows 19 c on the other endof the applicator 4. Rows 19 b and rows 19 c are symmetrically disposedwith a symmetry line 20 defined at a middle of the exemplary thermalablation applicator 4. Transducer arrays 17 (i.e., columns) are disposedas shown in previous illustrations of FIG. 3 and FIG. 4, and eachtransducer array 17 comprises aligned transducer elements 18 from allrows 19 b and rows 19 c. Optionally and as shown, adjacent transducerarrays 17 are electrically shunted two by two in order to reduce thenumber of output connections for the applicator. Rows 19 b and 19 c arearranged respectively in the position order from P₁ to P_(N) for rows 19b and from Q₁ to Q_(N) for rows 19 c. Furthermore, the row of positionP₁ is shunted to the row of position Q₁ to form a unique electricalconnection and so on in manner to divide by two the number of outputconnections for rows 19 b and 19 c. In operation, the bottom electrodesof the CMUT cells of the respective transducer arrays 17 are connectedtogether, and the top electrodes of the CMUT cells of the respectiverows 19 b and rows 19 c are connected together, so that the control ofthe active surfaces of the exemplary thermal ablation applicator 4 isidentical to control described with respect to the exemplary applicatorof FIG. 4. Advantageously, the exemplary thermal ablation applicator 4of FIG. 5 having transducer rows 19 b and transducer rows 19 c that canbe excited in shunted mode two by two expands the ablation volume(especially in long axis dimension) that can be treated with a singleapplicator 4.

FIG. 8 shows yet another embodiment of an ultrasonic thermal ablationapplicator 4, including array transducers 10 comprised of CMUT (notshown) elementary transducers that are arranged along a long axis of thearray transducers 10. The number of array transducers 10 of the thermalablation applicator 4 is dependent on the application and type of tumorto be treated, and this number may extend from eight to twelve,typically, for achieving a reasonable compromise. Twelve arraytransducers 10 mounted on the periphery of the thermal ablationapplicator 4 is preferable, but not so limited. Preferably, arraytransducers 10 are identical in shape and dimensions but may differ inCMUT arrangement on their active face. Array transducers 10 areelectrically connected to flexible electrical collectors 9 that provideelectric contacts of the CMUT elements to an external interface (notshown). Typically, a coaxial cable (not shown) is connected to interfacewith the system mainframe (not shown). The flexible electricalcollectors 9 are preferably comprised of flexible PCB circuits usingKapton® or any polyimide-based material with a thickness thinner than 25μm. As discussed below, the array transducers 10 may be assembleddirectly on an applicator body 14 as shown in FIG. 9A, or may bepre-assembled with a backing support 16 as shown in FIG. 9B prior tomounting on the applicator body 14. The backing support 16 can be madeup of acoustic absorbent materials such as particle filled resin,plastic, ceramic, or any other nonmetallic (i.e., transparent to x-raysand other medical imaging radiation) acoustic absorbent material. At adistal end of the thermal ablation applicator 4, a guiding piece 12 in asubstantially conical shape is provided as protection for the arraytransducer mounting. The guiding piece 12 has an opening 7 located at acenter position in alignment with a hollow channel 5 (see: FIG. 1A-FIG.1C) of the thermal ablation applicator 4. On the proximal end of thethermal ablation applicator 4 where the array transducers 10 terminate,a ring 11 is provided to secure an interface between the arraytransducers 10 and the flexible electrical collectors 9.

FIG. 8A shows a magnified view of the proximal end of applicator 4 whereassembly details are provided for the array transducers 10, the ring 11,and the flexible electrical collectors 9. More particularly, the ring 11is preferably mounted to the probe body or structure and secures a flexextension part in the vicinity of the array transducers 10. The flexibleelectrical collectors 9 can be made of thin polyimide PCBs (e.g., 12 μmthick polyimide film), with copper/gold plated tracks on one or bothsides.

FIG. 9A is a sectional view of one assembly of the exemplary thermalablation applicator 4 taken through plane 9-9 as shown in FIG. 8. Thefigure shows the assembly of array transducer components andconstruction details of the applicator 4 wherein a body 14 is providedwith the hollow channel 5. The body 14 may have a plurality of facesregularly disposed on its periphery to form a polygon. In order toachieve a smooth treatment volume geometry, a number of faces for thebody 14 may preferably range from eight units at a minimum and have anoptimum number of twelve, however no limitation is made on the number offaces, as the number will only be limited by available miniaturizationand integration process/technology. In the same spirit of design, acylindrical shape for the body 14 is ideally desirable, but thisinherently constrains the transducer to be made flexible and conformableat such a small diameter (3-4 mm). The array transducers 10 are disposedon external faces of the body 14 with optional acoustic absorbingmaterial 15 that also comprises electrical contacts. The electricalcontacts can be, for example, flexible printed circuit boards (flexiblePCB), as the thickness of flexible PCBs is thin as compared to the othercomponents. For clarity, for one skilled in the art, the flexible PCBsare sandwiched between the array transducers 10 and the external facesof the body 14. The optional absorbent material can be particle filledresins or rigid nonmetallic materials with high backscatteringproperties. Otherwise, the array transducers 10 may be directly securedto the body 14 with electrical contacts disposed there between. Thearray transducers 10 may be provided with a matching layer (not shown)laminated on a front surface to improve the acoustic performance andelectrical safety for patients. Finally, the exemplary thermal ablationapplicator 4 is covered with a protective layer 13 to complete theassembly. Advantageously, the protective layer 13 can be made up ofelectrically insulated silicon rubber or resin and preferably moldedonto the thermal ablation applicator 4 to obtain a cylindrical externalshape. As an alternative solution, a polygonal external section is alsopossible with the use of a flat thin electrically insulated protectivelayer that will be conformal to the front surfaces of the arraytransducers 10.

FIG. 10 shows, in yet another embodiment of the invention, an exemplarythermal ablation applicator 4 having a similar shape and dimensions tothe exemplary thermal ablation applicator 4 of FIG. 8. The exemplarythermal ablation applicator 4 is having different active portions thatcomprise equal number of transducer arrays 10, from the proximal todistal end of the applicator there are preferably and respectivelyportions 27, 29 and 28 that are mounted in adjacent manner. Portion 29is dedicated to thermal ablation operations as previously described andthe portions 27 and 28 can be equipped with other type of sensors ordetectors provided that they can be micro manufactured on substratescompatible with the dimensions herein required. As an example, CMUTs aremainly fabricated on a Si substrate, as are other sensors such as:pressure sensors, targeted bio-sensors (enzymes, antibodies and nucleicacids), chemical sensors, temperature sensors, and micro arrays ofelectrodes. In the exemplary thermal ablation applicator 4, portions 27and 28 can be provided with any of the previously mentioned sensors tocomplete the instrument upon clinical requirements or needs.

In still yet another embodiment (not shown but described with referenceto FIG. 10) wherein only either portion 27 or portion 28 is included inthe applicator 4, portion 29 is still present for thermal ablation andthe portion 27 or portion 28 is equipped with chemical sensors tomeasuring physiological parameters of the tissue in contact.

FIG. 11 shows, in yet one further embodiment, an exemplary thermalablation applicator 4 including thermal ablation operations portion 29,as well as portion 27 and portion 28. Portion 27 and portion 28 compriseintegrated nano laser oscillator emitters to allow in vivo sub-cellulartissue identification by near-infrared multi photon-induced autofluorescence microscopy. To allow photo sensitive nanoparticle delivery,the nano laser oscillator emitters are located on the periphery ofportion 27 and/or portion 28 to dispatch light energy to the surroundingstructure

What is claimed is:
 1. An interstitial ultrasound thermal ablation applicator to be inserted into tumor lesions for conformal treatment of inhomogeneous tumor lesions, comprising: a body having a longitudinal needle shape and a longitudinal axis, the body defining a hollow central channel along the longitudinal axis, the hollow central channel serving as a passage for biopsy needles or tools for aspiration of biologic materials or providing in-situ drug delivery; and a plurality of capacitive micromachined ultrasonic transducer (CMUT) array transducers externally mounted on said body and having on each array a number of separate elementary transducers linearly arranged and said CMUT array transducers are arranged side by side to form a pseudo cylindrical shape and having azimuth plans parallel to the longitudinal axis of the body; said CMUT array transducers are having predetermined elevation dimension defined for steering emitted ultrasonic energy to obtain a conformal volume treatment of the tumor lesions.
 2. The interstitial ultrasound thermal ablation applicator according to claim 1, wherein the CMUT array transducers are wholly covered with electrically insulating protective layers.
 3. The interstitial ultrasound thermal ablation applicator according to claim 1, wherein body is made up of organic or mineral material.
 4. The interstitial ultrasound thermal ablation applicator according to claim 1, wherein an elevation dimension of said CMUT array transducers are determined to not excess three (3) water equivalent wavelengths.
 5. The interstitial ultrasound thermal ablation applicator according to claim 1, wherein a thickness of said CMUT array transducers is provided at less than 100 microns, so as to conform with an external surface of the body.
 6. The interstitial ultrasound thermal ablation applicator according to claim 1, further comprising a biocompatible protection film covering the body and the CMUT array transducers.
 7. An interstitial ultrasound thermal ablation applicator to be inserted into tumor lesions for conformal treatment of inhomogeneous tumor lesions, comprising: a body having a longitudinal catheter shape and a longitudinal axis; a plurality of capacitive micromachined ultrasonic transducer (CMUT) array transducers mounted on said body, arranged side by side to form a cylindrical shape, having azimuth plans parallel to the longitudinal axis of the body, each of the said CMUT array transducers having elevation dimensions predetermined to steer emitted ultrasonic energy to control smoothness of a resulting ablation volume; and at least one integrated sensing device mounted within the transducing area to monitor at least one of the physical/physiological parameters of the surrounding tissue.
 8. The interstitial ultrasound thermal ablation applicator for the treatment of inhomogeneous tumor lesions according to claim 7, wherein the integrated sensing device is temperature sensor.
 9. The interstitial ultrasound thermal ablation applicator for the treatment of inhomogeneous tumor lesions according to claim 7, wherein the integrated sensing device is a pressure sensor.
 10. The interstitial ultrasound thermal ablation applicator for the treatment of inhomogeneous tumor lesions according to claim 7, wherein the integrated sensing device is a gas sensor.
 11. The interstitial ultrasound thermal ablation applicator for the treatment of inhomogeneous tumor lesions according to claim 7, wherein the integrated sensing device is a biosensor for detection of enzymes, antibodies or nucleic acids.
 12. The interstitial ultrasound thermal ablation applicator for the treatment of inhomogeneous tumor lesions according to claim 7, wherein the integrated sensing device is a laser emitter.
 13. An interstitial ultrasound thermal ablation applicator for treatment of inhomogeneous tumor lesions, comprising: a body having a longitudinal catheter shape and a longitudinal axis; a plurality of capacitive micromachined ultrasonic transducer (CMUT) array transducers mounted on said body, arranged side by side to form a cylindrical shape, having azimuth plans parallel to the longitudinal axis of the body, each of the said CMUT array transducers having elevation dimensions predetermined to steer emitted ultrasonic waves to control smoothness of a resulting ablation volume; an integrated sensing device for monitoring at least one of a physical/physiological parameters of the surrounding tissue; and an integrated Lab-on-Chip (LoC) device located within a surface of one of the said CMUT array transducers for in-situ analyzing of tissue.
 14. The interstitial ultrasound thermal ablation applicator for treatment of inhomogeneous tumor lesions according to claim 13, wherein the LoC device is a microfluidic device designed for cytometry assays and biological assays.
 15. An electronic driving method for controlling interstitial ultrasound thermal ablation applicator having multiple independent transducer elements arranged in rows and columns and being disposed on a periphery of a cylindrical ultrasound thermal ablation applicator, such method comprising: controlling focal parameters of each row and column of transducer elements; and controlling contribution of each row and column of transducer elements in a manner to provide a conformal ablated volume.
 16. The electronic driving method according to claim 15, further comprising: shunting electrically adjacent transducer elements two by two in each respective row; and controlling the transducer elements in columns independently to achieve conformal volume sonication/treatment.
 17. The electronic driving method according to claim 15, further comprising: shunting together top electrodes of the transducer elements in each respective row, such that all rows are electrically isolated; shunting together bottom electrodes of the transducer elements in each respective column, such that all columns are electrically isolated; and activating desired transducer elements by connecting the top electrodes of a selected row and the bottom electrodes of a selected column to a power supply simultaneously to polarize the desired transducer elements located in both the selected rows and the selected columns.
 18. The electronic driving method according to claim 15, further comprising: shunting together top electrodes of the transducer elements in each respective row, such that all rows are electrically isolated and connecting to an alternative voltage driving system; shunting together bottom electrodes of the transducer elements in each respective column, such that all columns are electrically isolated; and connecting to a direct current voltage controller modulating output of a desired transducer element by applying a given DC voltage and AC voltage.
 19. The electronic driving method according to claim 15, further comprising: activating, by separate DC bias controllers, specific subgroups of elements or arrays of the device, such that a DC bias voltage level delivered to a specific subgroup of elements having a common bottom electrode may be used to modulate acoustic output of the specific subgroup of elements.
 20. The electronic driving method according to claim 15, wherein the rows are disposed symmetrically with a symmetry line at a middle of the interstitial ultrasound thermal ablation applicator, wherein the rows are arranged in a position order from P₁ to P_(N) and Q_(N) to Q₁, respectively, around the symmetry line, the method further comprising: shunting together top electrodes of the transducer elements forming a row P_(X) and a row Q_(X) of same order, such that rows of different orders are electrically isolated; arranging rows P and rows Q in reverse chronology so as to obtain the last order row P_(N) adjacent to the last order row Q_(N) and therefor first order row P₁ and first order Q₁ are located at opposite ends of the interstitial ultrasound thermal ablation applicator; shunting together bottom electrodes of the transducer elements forming in each respective column, such that all columns are electrically isolated; and activating a desired transducer element by connecting the top electrodes of a selected row and the bottom electrodes of a selected column to a power supply simultaneously to polarize the desired transducer element located in both the selected row and the selected column.
 21. A method of providing thermal ablation of a tissue region by an interstitial procedure using an interstitial ultrasound thermal ablation applicator comprising a plurality of ultrasonic transducers, comprising: inserting and positioning the interstitial ultrasound thermal ablation applicator at a center of one of incriminated tissue and a tumor; applying electrical actuation individually to the plurality of ultrasonic transducers, each of the plurality of ultrasonic transducers having respective custom focal characteristics; controlling ultrasonic energy supplied and treatment duration for each of the plurality of ultrasonic transducers to control tissue temperature elevation and distribution; controlling ultrasonic frequency, phase, and DC bias to control tissue temperature elevation and distribution; and removing ablated material from a treatment site for assessment.
 22. The method of providing thermal ablation of a tissue region according claim 21, the elements integrated on the same applicator allow combining multiple ultrasound beams at various frequencies over a broad continuous spectrum (e.g. 2-30 MHz) for performing conformal thermal ablation.
 23. The method of providing thermal ablation of a tissue region according claim 21, the elements integrated on the same applicator allow modulating the frequency, power and phase of the excitation according to the feedback of a treatment monitoring system for performing conformal thermal ablation.
 24. The method of providing thermal ablation of a tissue region according claim 21, wherein the procedure is performed under magnetic resonance (MR) scanning to monitor local temperatures.
 25. The method of providing thermal ablation of a tissue region according claim 21, wherein the interstitial ultrasound thermal ablation applicator has a catheter shape with a diameter smaller than 4 mm so as to avoid damage to healthy tissue during insertion. 